title: Self-assembling micelle-like nanoparticles based on phospholipid-polyethyleneimine conjugates for systemic gene delivery.
abstract: With few exceptions, where local administration is feasible, progress towards broad clinical application of gene therapies requires the development of effective delivery systems. Here we report a novel non-viral gene delivery vector, 'micelle-like nanoparticle' (MNP) suitable for systemic application. MNP were engineered by condensing plasmid DNA with a chemical conjugate of phospholipid with polyethylenimine (PLPEI) and then coating the complexes with an envelope of lipid monolayer additionally containing polyethylene glycol-phosphatidyl ethanolamine (PEG-PE), resulting in spherical 'hard-core' nanoparticles loaded with DNA. MNP allowed for complete protection of the loaded DNA from enzymatic degradation, resistance to salt-induced aggregation, and reduced cytotoxicity. MNP also demonstrated prolonged blood circulation and low RES accumulation. Intravenous injection of MNP loaded with plasmid DNA encoding for the Green Fluorescence Protein (GFP) resulted in an effective transfection of a distal tumor. Thus, MNP provide a promising tool for systemic gene therapy.
authors.affiliation: Department of Pharmaceutical Sciences, Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Boston, MA 02115, USA.
authors.forename: Young Tag
authors.initials: YT
authors.lastname: Ko
authors.forename: Amit
authors.initials: A
authors.lastname: Kale
authors.forename: William C
authors.initials: WC
authors.lastname: Hartner
authors.forename: Brigitte
authors.initials: B
authors.lastname: Papahadjopoulos-Sternberg
authors.forename: Vladimir P
authors.initials: VP
authors.lastname: Torchilin
mesh_terms: D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival; D004247:DNA / Q000008:administration & dosage / Q000493:pharmacokinetics; D015870:Gene Expression; D018014:Gene Transfer Techniques; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008823:Micelles; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D041681:NIH 3T3 Cells; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D010713:Phosphatidylcholines / Q000737:chemistry; D010743:Phospholipids / Q000737:chemistry*; D010767:Phosphorylcholine / Q000031:analogs & derivatives / Q000737:chemistry; D010957:Plasmids / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D011094:Polyethyleneimine / Q000737:chemistry*; D014018:Tissue Distribution; D014162:Transfection
chemical_list: C528536:1-palmitoyl-2-azelaoyl-sn-glycero-3-phosphocholine; D008823:Micelles; D010713:Phosphatidylcholines; D010743:Phospholipids; D010767:Phosphorylcholine; D049452:Green Fluorescent Proteins; D011094:Polyethyleneimine; D004247:DNA; C028694:1-palmitoyl-2-oleoylphosphatidylcholine